Wednesday, June 26, 2013

Called DILD1T, this is a 40 person clinical trial. It started in March 2013, and is expected to finish in January 2015. It is enrolling adults who have had type-1 diabetes for 3-24 months (so not just honeymooners) in Addenbrooke’s Hospital, Cambridge, UK. Currently, it is only 12% enrolled, so they have a ways to go. I'm treating this as a phase-II trial, because of it's size and because Proleukin has already been tested twice in type-1 diabetics (that I know of).

I think that this study involves only one subcutaneous injection (like an insulin injection).

Here is the justification for the study. The quote is from the researchers, but I've removed some of the medical language:

The researchers view this study as looking for the optimal dose as a prelude to doing a large phase-III trial. This is a classic goal of many phase-II trials. This trial is funded by the Welcome Trust (a big UK operation), JDRF, and the NHS Foundation Trust (which I think is the UK government).

I've been following DiaPep 277 for as long as I've been following type-1 diabetes cures. When I started, it was already in phase-II trials. Recently Andromeda Biotech Ltd, the company developing it, has published some phase-III results, and (most recently) some extended phase-III results. These extended results are from people who were in the phase-III trial for two years, and then continued with the treatment for an additional two years. The two year extension was "open label", meaning that the patients and doctors knew they were getting the treatment; it was not blinded.

Unfortunately, the results are decidedly mild. People's A1C numbers dropped by 0.6 (from an average of 7.6 to an average of 7.0. In terms of improvement of treatment, that's not bad. I think there is a market for a drug that would lower A1C numbers that amount, but it is not a cure. There is always hope that future improvements in the treatment will lead to even better A1C improvements (which I think is likely), or even improvements so great they lead to a cure (which I think is very unlikely). But currently, this is an adjunct treatment, not a cure. So I expect to stop covering DiaPep 277, unless I see results much larger than are seen here.

This news comes from a human trial in multiple sclerosis (MS) patients. Basically, researchers were able to "reset" the body's immune system, to lower the autoimmunity reaction (the body's attacking it's own cells) by 50%.-75%. This was in a 9 person phase-I trial in Germany.

To understand why that is important, a little background is needed. Most researchers believe that MS and Type-1 are related diseases. In both cases the immune system mistakenly attacks the body's own cells. In Type-1, it attacks beta cells in the pancreas, and in MS it attacks the myelin sheaths of nerve cells, however the underlying autoimmunity reaction is similar.

Prior to testing on people, this method was tested in mice who had MS and in mice who had type-1 diabetes, and worked on both groups of mice. However, the human trials were MS only. But obviously, trials in type-1 diabetic people could be done as well. In my opinion, should be done.

The idea of resetting (or rebooting) the body's immune system has been tried on type-1 diabetics, and it was successful. Some of the treated type-1 diabetics did not have to inject insulin for years afterwards. However, the risk involved is high enough, that these treatments have never moved forward. At least three different teams (in Brazil, Poland, and China) have run similar trials and gotten similar results. I have blogged about them before:http://cureresearch4type1diabetes.blogspot.com/search/label/Burt

Although it is hard to draw a direct comparison, it sounds like the procedure being tested here is much safer, but slightly less effective than the procedure used by Burt, Snarski, Li, etc. Of course, it might be refined over time to make it more effective or safer, or both.

In the past, I've posted on my blog what I call a "non-conflict of interest statement" which is this:

I don't work for a company involved in medical research; I never have.

I don't get paid in any way by any company doing medical research; I never have. And that includes free samples, free travel, or free anything.

None of the hours that I have put into my blog, or the posts that I make to any web site, has ever been paid for, nor have I gotten anything free. (Except for some very nice and heart felt thank-you emails, and those are worth more than money.)

I'm now adding a fourth bullet point:

My daughter has type-1 diabetes and participates in clinical trials. She usually gets some money for participating. I sometimes report on trials that she participates in. For several reasons, I don't generally reveal what studies she enrolled in (or tried to enroll).

Why not, you ask? A couple of reasons. First of all, her participation is a two step process. My wife and I decide the research is safe and that she can participate, and then she decides if she wants to participate. Therefore, she selects different studies than I would select. For example, she prefers studies in the summer, and studies that pay well. I don't want people coming back to me and saying why did she participate in study X rather than study Y? Second, I get important information from researchers. I don't want researchers thinking, "his daughter was in Dr. X's trial, but not mine, why is that?" (Truthfully, the answer is usually, Dr. X paid better, or required less time, or was more convenient, but I don't want to be explaining that.) Thirdly, I don't want readers of this blog to be thinking "Joshua's daughter isn't in trial X, why should my child be in that one?" or the reverse "Josh's daughter is in trial X, I should get my kid in there, also!" Our kids are different, and participating in a trial should always be personal decision. And finally, even participating in a trial might make public health information about my daughter that I don't want public. For example, enrollment might only be open to people who have a particular side effect, or don't have that side effect, or who are still generating some insulin, or whatever.In the last 5 years, I have only blogged on one study that my daughter participated in. I would expect to blog on only a couple in the next 5 years, so this is a rare thing.

Joshua LevyAll the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

Saturday, June 22, 2013

Some researchers in Boston made a big splash recently by claiming to find the "root cause" of type-1 diabetes. I've gotten at least two emails asking for my thoughts on the research, so here they are.

One thing that I try to do, is to read the original paper, or at least the abstract, and then describe what the researchers did, what they found, and why it is important. I've found that the original research often contains valuable information that doesn't make it into press releases, news articles, blog postings, etc. So I try hard to find that original work.

Unfortunately, I can't do that for this paper. I've read the abstract a couple of times, and I can't make heads or tails of it. The abstract assumes a level of knowledge way beyond me. One thing that did make me nervous was this: it looks like this research was done on people and mice who had transplants to treat type-1 diabetes, and they studied how those people's bodies attacked the transplanted cells. This makes me nervous because the immune system's attack on a transplanted organ is proper. It's a foreign invader, after all. This is different than the immune system's attack on it's own pancreas, which is an error. I'm not sure learning about the causes of one, is going to teach us what causes the other. On the other hand, I might be totally misunderstanding what they were doing. The abstract is opaque to me.

How important is this?

I don't know. I don't think anyone knows, as yet. It often takes a few years to confirm that a breakthrough really is the big breakthrough that everyone hoped it was at the start. Even after we know that this is a big breakthrough, we don't know if it will lead to a cure or not. The discovery of the smallpox virus (for example) did not lead to the discovery of a cure for smallpox (and the first smallpox vaccine predated knowledge of the smallpox virus).

In the future, if this leads to a cure (or preventative) for type-1 diabetes, then we will be able to look back and say, "this really was that important". But there is no reasonable way for us to look into the future and know that this discovery is that important right now.

(I know that's kind of depressing. Some people react to that by not donating money to research, because they never know which research is going to lead to a cure. I view it the exact opposite, that it is important to give money to research, so that as many different options can be funded as possible, specifically because we don't know which will lead to a cure.)

What does this mean to me?

I care about a cure for type-1 diabetes, so what does this discovery mean to me? Basically, a lot more research. In order to get from a discovery of root cause to a cure, at least three things need to happen. (a) they need to be sure the discovery is correct and use that discovery to figure out a cure. (b) they need to test that cure in petri dishes, tissue samples, and animals. (c) they need to test it in people. Now (a) often takes a few years, although sometimes less, and (b) can take anywhere from years to decades, and (c) takes at least 10 years. So making a few reasonable guesses, I would expect any cure that comes from this discovery to arrive in 15+ years (for an optimistic guess) to 25+ years (for a more reasonable guess). If this discovery pans out as being important. And that is a big "if".

One last word.

Curtis Lomax said "This one smells like a lot of hype." I agree, and I couldn't put it better myself. In fact, I'm linking to the Lynyrd Skynyrd song "That Smell" as the theme song for this posting:http://www.youtube.com/watch?v=sV_toedW2L0

Joshua LevyAll the views expressed here are those of Joshua Levy, and nothing here is official JDRF or JDCA news, views, policies or opinions. My daughter has type-1 diabetes and participates in clinical trials, which I sometimes blog on. My blog contains a more complete non-conflict of interest statement. Thanks to everyone who helps with the blog.
Clinical Trials Blog: http://cureresearch4type1diabetes.blogspot.com
Cured in Mice Blog: http://t1dcuredinmice.blogspot.com/

My Most Important Posts

Follow by Email

This blog discusses cures and preventatives for type-1 diabetes that are either in human trials or just about to start. Treatments for diabetes are not generally discussed here, unless they can turn into a cure or a preventative. My definition of a cure is this:1. Blood sugar control without testing and with doctor's visits 4 times a year, or less. Any cure must result in an average lifespan close to normal.2. Does not require a lifetime of immunsuppressive drugs, so it is not trading one treatment for another. (but a couple of operations, or a short course of drugs is OK)Obviously, this is my personal definition of a cure; yours may differ.Because a cure for type-1 diabetes is likely to involve a combination of several different drugs or treatments, I try to follow research into anything which may be an important part of the cure.

My Non-Conflict of Interest Statement

I don't work for a company involved in medical research; I never have.

I don't get paid in any way by any company doing medical research; I never have. And that includes free samples, free travel, or free anything. I do sometimes participate in market research studies or focus groups, and they sometimes pay.

None of the hours that I have put into my blog, or the posts that I make to any web site, has ever been paid for. (Except for some very nice and heart felt thank-you emails, and those are worth more than money.)

My daughter has type-1 diabetes and participates in clinical trials. I sometimes report on trials that she participates in, but I do not reveal her participation because I consider her medical history to be private.

I sometimes "beta test" new software or devices involved in type-1 diabetes. When I'm blogging about something where I have been given special access, I say so.

In the past I have volunteered with JDRF, The NIIB Project, and I currently am a fellow with JDCA. JDRF and NIIB Project was completely unpaid. JDCA has given me equipment that I use to help my blogging.

Over the years my daughter has used several types of insulin, several types of meters, and pumps made by different manufacturers. I don't always mention if I'm blogging about a company who's products she uses now or in the past (there are so many).